Title | TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Hossain MB, Shifat R, Johnson DG, Bedford MT, Gabrusiewicz KR, Cortes-Santiago N, Luo X, Lu Z, Ezhilarasan R, Sulman EP, Jiang H, Li SSC, Lang FF, Tyler J, Hung M-C, Fueyo J, Gomez-Manzano C |
Journal | Sci Adv |
Volume | 2 |
Issue | 4 |
Pagination | e1501290 |
Date Published | 2016 04 |
ISSN | 2375-2548 |
Keywords | Angiotensin I, Cell Line, Tumor, DNA Damage, DNA End-Joining Repair, Histones, Humans, Protein Binding, Protein Transport, Proto-Oncogene Proteins c-abl, Radiation Tolerance, Radiation, Ionizing, Receptor, TIE-2, Tyrosine |
Abstract | DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier. H4Y51 constitutes the first tyrosine phosphorylation of core histones recognized by ABL1, defining this histone modification as a direct signal to couple genotoxic stress with the DNA repair machinery. |
DOI | 10.1126/sciadv.1501290 |
Alternate Journal | Sci Adv |
PubMed ID | 27757426 |
PubMed Central ID | PMC5065225 |
Grant List | P30 CA016672 / CA / NCI NIH HHS / United States R01 CA079648 / CA / NCI NIH HHS / United States R01 CA095641 / CA / NCI NIH HHS / United States R01 NS069964 / NS / NINDS NIH HHS / United States P50 CA127001 / CA / NCI NIH HHS / United States |
Related Faculty:
Jessica K. Tyler, Ph.D.